The invention relates to medical devices associated with agents that inhibit restenosis.
Prostheses, i.e., prosthetic devices, are used to repair or replace damaged or diseased organs, tissues and other structures in humans and animals. Prostheses must be generally biocompatible since they are typically implanted for extended periods of time. Prostheses can be constructed from natural materials such as tissue, synthetic materials or a combination thereof.
Invasive procedures are commonly used to treat various forms of cardiovascular disease. Routine procedures include angioplasty, atherectomy, insertion of stents and laser surgery. However, damage resulting from this contact with a patient""s blood vessels can result in restenosis, the blockage of blood vessels. In particular, balloon angioplasty and atherectomy are associated with relatively high incidents of restenosis in the three to six months following the procedure.
A common procedure for treating arteriosclerosis is balloon angioplasty. To perform balloon angioplasty, a catheter is guided through an artery to a location with restricted flow. A balloon catheter is then inflated to a pressure between, for example, 3 and 6 atmospheres for about 60 seconds. The inflation of the balloon cracks the plaque lining the vessel walls stretching the arterial wall, so that the lumen of the artery is expanded following the inflation of the balloon. The increased lumen allows for increased blood flow, but restenosis can result in subsequent loss of blood flow through the lumen.
Vascular stents involve structures that are expanded within a blood vessel to maintain or expand the lumen of the vessel. While intravascular stents can be used to successfully achieve increased internal lumen diameter, stent restenosis also can result in intimal thickening that reduces the effectiveness of the stent.
Restenosis is characterized by platelet aggregation and adhesion, and by smooth muscle cell migration and proliferation, which individually or together result in the narrowing of the vessel lumen. The narrowing of the vessel restricts vasodilation and causes an increase in blood pressure. The smooth muscle cells along the vessel lining being proliferating within two to three days of disruption of the vessel and continue for several days. In addition to vessel narrowing, restenosis can lead to blood clotting, which further threatens stroke, lung damage and heart damage if the blood clots travels from the formation site. Some approaches for the prevention or treatment of restenosis include the delivery of radioactive compounds or of nitric oxide, which is implicated in platelet accumulation.
In a first aspect, the invention pertains to a medical device suitable for implantation including a biocompatible material and a plurality of exogenous biological macromolecules bound to the biocompatible material. The exogenous biological macromolecules store a therapeutic agent which acts to inhibit restenosis.
In another aspect, the invention pertains to a medical device suitable for implantation comprising a biocompatible material and a plurality of exogenous storage structures bound to the biocompatible material. The exogenous storage structures store isotopically enhanced radioactive metal ions.
In a further aspect, the invention pertains to a method for inhibiting restenosis comprising binding an exogenous storage structure to a biocompatible material forming at least a portion of a vascular prosthesis. The storage structure comprises a biological macromolecule. The method further includes associating the storage structure with a therapeutic agent which acts to inhibit restenosis.
In addition, the invention pertains to a medical device suitable for implantation comprising a biocompatible material and a therapeutic agent covalently bonded to the biocompatible material. The therapeutic agent actsa to inhibit restenosis.
In another aspect, the invention pertains to a medical device including an expandable structure and therapeutic particles on the surface of the expandable structure. The therapeutic particles include a therapeutic agent that acts to inhibit restenosis.
Furthermore, the invention pertains to a method of producing a medical device comprising applying therapeutic particles to the exterior of an expandable structure. The therapeutic particles include a therapeutic agent that inhibits restenosis.